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我国甲状腺癌的发病率日益增加,约90%为分化型甲状腺癌(differentiated thyroid carcinoma,DTC)[1]。DTC在初诊时发生远处转移的概率为1%~23%[2],此类患者预后较差。血清甲状腺球蛋白(thyroglobulin,Tg)水平是为DTC患者制定治疗计划及治疗后随访的重要参考指标。术后131I治疗前血清预先刺激性Tg(preablative stimulated thyroglobulin,ps-Tg)是指术后未服或停服左旋T4后,TSH水平升高(>30 μIU/mL)状态下测定的血清Tg水平,其水平高低与肿瘤术后残留情况及初始治疗后疾病的缓解、持续和复发密切相关。2015年美国甲状腺学会《成人甲状腺结节与分化型甲状腺癌诊治指南》[3](简称2015版ATA指南)强调了高ps-Tg水平在131I治疗前风险评估中的重要性。本文旨在研究术后首次血清ps-Tg水平对DTC发生远处转移的预测价值。
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M0组共纳入患者85例,131I治疗的剂量为(3.77±0.41) MBq;M1组共纳入患者28例,131I治疗的剂量为(4.23±0.86) MBq。其他具体数据见表1。
分组
(例数)性别(例) 年龄(岁) 病理类型(例) 手术至首次
检测ps-Tg
的时间
(个月)T分期(例) N分期(例) 治疗剂量分组(例) TSH
(IU/mL)
M(P25~P75)ps-Tg
(ng/mL)
M(P25~P75)TgAb
(mIU/L)
M(P25~P75)男性 女性 滤泡癌 乳头
状癌T3 T4 N1a N1b 低剂
量组高剂
量组M0组(85) 21 64 45.45±10.92 0 85 3.18±2.52 59 16 71 7 81 4 100.00
(81.80~100.00)1.95
(0.70~6.98)0.40
(0.10~1.20)M1组(28) 11 17 43.04±14.93 4 24 2.43±0.88 26 12 14 21 20 8 100.00
(84.92~100.00)95.05
(6.98~278.47)0.40
(0.10~1.88)检验值 χ2=2.206 t=36.985 χ2=12.588 t=111 χ2=1.420 χ2=12.588 χ2=12.851 U=1044.5 U=417.5 U=1141.5 P值 0.138 0.436 0.003 0.127 0.233 0.003 0.002 0.316 0.000 0.746 注:表中,M0组:未发现转移的患者;M1组:除外颈部及纵隔淋巴结有远处转移的患者;低剂量组:131I治疗剂量为(3.77±0.41) MBq;高剂量组:131I治疗剂量为(4.23±0.86) MBq。DTC:分化型甲状腺癌;ps-Tg:预先刺激性甲状腺球蛋白;TSH:促甲状腺激素;TgAb:甲状腺球蛋白抗体。 表 1 2组DTC患者的临床资料比较
Table 1. Comparison of differentiated thyroid carcinoma patients’ basic clinical data between 2 groups
在M1组的28例患者中,19例为双肺转移,6例为骨转移,2例为双肺转移并骨转移,1例为双肺转移、骨转移并盆腔转移。典型病例的131I Rx-WBS图和SPECT/CT显像图见图1,该患者在131I治疗前ps-Tg水平较高,为76.54 ng/mL,CT未发现转移灶,但是131I治疗后行Rx-WBS时发现右侧坐骨存在放射性浓聚异常,这提示存在转移。由表1可见,M1组的病理类型、颈部淋巴结转移情况及131I治疗剂量与M0组比较,差异有统计学意义;但性别、年龄、肿瘤分期、手术至首次检测ps-Tg时间、TSH水平和TgAb水平的比较,差异无统计学意义。
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ps-Tg预测远处转移的ROC曲线分析结果见图2。ps-Tg水平ROC曲线下面积为 0.825,标准误为0.057,差异有统计学意义(95%CI:0.713~0.936,P=0.000);根据ROC曲线分析结果,以约登指数(灵敏度+特异度−1)为纵坐标、ps-Tg水平为横坐标作图,得到约登指数最大为 0.632,该点对应的ps-Tg水平为28.80 ng/mL。以ps-Tg水平28.80 ng/mL为DCP值,对应的灵敏度、特异度和准确率分别为 71.4%、91.8%和86.7%。
分化型甲状腺癌术后首次血清刺激性Tg水平对远处转移的预测价值
Predictive value of postoperative initial stimulated thyroglobulin level on distant metastasis of differentiated thyroid carcinoma
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摘要:
目的 探讨分化型甲状腺癌(DTC)患者术后首次血清预先刺激性甲状腺球蛋白(ps-Tg)水平对远处转移的预测价值。 方法 收集2016年8月至2017年8月首次行131I治疗的113例DTC患者的临床资料,其中男性32例、女性81例,年龄15~68(44.85±12.01)岁。将患者分为无远处转移(M0)组和远处转移(M1)组。所有患者在未服或停服左旋甲状腺素4周后,行甲状腺功能与抗体水平等检测,行131I治疗后全身显像(Rx-WBS)和局部SPECT/CT断层融合显像。采用χ2检验、独立样本t检验和Mann-Whitney秩和检验对比2组患者的基本资料;采用Mann-Whitney秩和检验比较2组之间ps-Tg水平的差异;非参数法建立ps-Tg水平的受试者工作特征(ROC)曲线,获得最佳诊断界值点(DCP)。 结果 M0组(85例)与M1组(28例)的病理类型、颈部淋巴转移情况及131I治疗剂量均存在差异,且差异有统计学意义(χ2=12.588、12.588、12.581,P=0.003、0.003、0.002);而性别、年龄、肿瘤分期、手术至首次检测ps-Tg的时间、促甲状腺激素和甲状腺球蛋白抗体水平的差异均无统计学意义。2组患者ps-Tg水平的M(P25~P75)分别为1.95(0.70~6.98) ng/mL和95.05(6.98~278.47) ng/mL,且差异有统计学意义(U=417.5,P=0.000)。ps-Tg水平ROC曲线下面积为0.825(95%CI:0.713~0.936),灵敏度、特异度和准确率分别为71.4%、91.8% 和86.7%,DCP为28.80 ng/mL。 结论 DTC术后首次血清ps-Tg水平对预测DTC远处转移有重要价值。 -
关键词:
- 分化型甲状腺癌 /
- 甲状腺球蛋白 /
- 碘放射性同位素 /
- 肿瘤转移 /
- 单光子发射计算机体层摄影术
Abstract:Objective To investigate the predictive value of postoperative initial stimulated thyroglobulin(ps-Tg) level on the distant metastasis of differentiated thyroid carcinoma(DTC). Methods A total of 113 patients who suffered from DTC and underwent first radioactive iodine(RAI) therapy from August 2016 to August 2017 were identified. Of these patients, 32 were males and 81 were females. Their ages ranged from 15 years to 68 years (44.85±12.01 years). The patients were classified into a non-distant metastasis(M0) group and a distant metastasis(M1) group. The biochemical parameters of thyroid function and thyroid antibodies were evaluated after 4 weeks of levothyroxine withdrawal. After RAI therapy, whole body imaging and local SPECT/CT were performed. The basic data of the two groups were compared via a chi-square test, Student's t test, and a Mann-Whitney rank-sum test. ps-Tg values between M0 and M1 were also compared via the Mann-Whitney rank-sum test. An receiver operating characteristic(ROC) curve was drawn and analyzed to evaluate the predictive value of ps-Tg, and a diagnostic critical point(DCP) was obtained. Results Differences in pathological type, cervical lymph node metastasis, and RAI dose were observed between M0(85 cases) and M1(28 cases) (χ2=12.588, 12.588, 12.581; P=0.003, 0.003, 0.002). No significant differences were found in gender, age, tumor stage, and time from surgery to the first measurement of Tg, TSH, and TgAb between the two groups. The mean values M(P25~P75) of ps-Tg levels in the two groups were 1.95(0.70–6.98) and 95.05 (6.98–278.47) ng/mL. A significant difference was present between the two groups(U=417.5, P=0.000). The area under the ROC curve of ps-Tg levels was 0.825(95%CI: 0.713–0.936), with a sensitivity of 71.4%, a specificity of 91.8%, and an accuracy of 86.7%. The cut-off value of DCP was 28.80 ng/mL. Conclusion The initial ps-Tg level is a meaningful indicator for predicting the distant metastases of DTC. -
表 1 2组DTC患者的临床资料比较
Table 1. Comparison of differentiated thyroid carcinoma patients’ basic clinical data between 2 groups
分组
(例数)性别(例) 年龄(岁) 病理类型(例) 手术至首次
检测ps-Tg
的时间
(个月)T分期(例) N分期(例) 治疗剂量分组(例) TSH
(IU/mL)
M(P25~P75)ps-Tg
(ng/mL)
M(P25~P75)TgAb
(mIU/L)
M(P25~P75)男性 女性 滤泡癌 乳头
状癌T3 T4 N1a N1b 低剂
量组高剂
量组M0组(85) 21 64 45.45±10.92 0 85 3.18±2.52 59 16 71 7 81 4 100.00
(81.80~100.00)1.95
(0.70~6.98)0.40
(0.10~1.20)M1组(28) 11 17 43.04±14.93 4 24 2.43±0.88 26 12 14 21 20 8 100.00
(84.92~100.00)95.05
(6.98~278.47)0.40
(0.10~1.88)检验值 χ2=2.206 t=36.985 χ2=12.588 t=111 χ2=1.420 χ2=12.588 χ2=12.851 U=1044.5 U=417.5 U=1141.5 P值 0.138 0.436 0.003 0.127 0.233 0.003 0.002 0.316 0.000 0.746 注:表中,M0组:未发现转移的患者;M1组:除外颈部及纵隔淋巴结有远处转移的患者;低剂量组:131I治疗剂量为(3.77±0.41) MBq;高剂量组:131I治疗剂量为(4.23±0.86) MBq。DTC:分化型甲状腺癌;ps-Tg:预先刺激性甲状腺球蛋白;TSH:促甲状腺激素;TgAb:甲状腺球蛋白抗体。 -
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